The transmission of malaria parasites by Anopheles mosquitoes presents a serious obstacle for effective malaria control. In areas of Africa where Plasmodium falciparum malaria is endemic, residents typically receive from 1 to greater than 1,000 bites per year from infective mosquitoes. Much of the geographic and seasonal variation in the incidence of malaria in humans is determined by the dynamics of vector populations. Available methods of drug treatment and vector control are ineffective for eliminating infection and disease due to malaria. Integral to the development of multi-stage vaccines against malaria is the need for expanded research on transmission-blocking vaccines. Current efforts to develop transmission-blocking vaccines specific for stages of malaria parasites that occur in the vector need to be complemented by research on anti-vector vaccines for killing mosquitoes and vaccines that target essential mosquito-related interactions with sporogonic-stage parasites. Specifically for Africa, an anti-vector vaccine is biologically relevant because the major vectors in the Anopheles gambiae complex and Anopheles funestus feed primarily (greater than 90 percent) on humans. A potent mosquito-killing vaccine could be devastating to local vectors because they typically blood-feed every 2 to 3 days, and have a lifetime potential for feeding on 10 or more humans. This Competing Continuation seeks practical solutions for blocking malaria parasite transmission at the level of the vector. The specific aims of the proposal are: 1) to employ phage-display recombinant antibody screening strategies in identifying candidate antigens and epitopes in Anopheles gambiae mosquitoes for the development of vaccines to directly kill vector species of mosquitoes, 2) to identify candidate antigens and epitopes in oocysts of Plasmodium falciparum parasites for the development of transmission-blocking vaccines, 3) to identify factors influencing the survival and infectivity of sporozoites in mosquitoes, and 4) to determine the influence of the mosquito midgut environment and associated microflora on the early stages of sporogonic development. Overall, the plan emphasizes biologically relevant solutions to the problems of malaria and involves research linkages with programs on malaria vectors and transmission in Africa.